Novel model of cerebrospinal fluid dynamics based on hemodynamically driven cyclic brain compliance variation

This study provides a novel explanation for the CerebrQ-Spinal Fluid (CSF) flow pattern observed in phase contrast cine-MRJ studies. CSF dynamics has been traditionally explained as a bulk flow from the site of production to the site of absorption. Studies done with phase contrast cine-MRI show a more complex CSF movement, that is not explainable by the bulk flow paradigm. This study describes a mechanism explaining how the energy delivered by the heart in each cycle is responsible not only for the blood flow, but also for the CSF circulation. This mechanism is based on a cyclic variation of brain compliance, dependent on the blood volume inside the brain vessels. As the cardiac cycle changes the blood volume inside the vessels, it also conditions a compliance cycle of the brain tissue. For better comprehension of the mechanism, a conceptual model, mathematical model and computer model are described. To capture the essence of CSF dynamics a three compartmental model is created representing: the ventricular system, the intracranial subarachnoideal space, and the spinal subarachnoideal space. The implemented driving function represents the blood volume variation with time produced by the cardiac cycle. In turn it detennines cyclic changes in brain parenchyma compliance. Brain parenchyma compliance changes as a function of the blood volume inside the brain vessels; therefore, during systole the compliance diminishes, during diastole compliance increases. As brain tissue compliance changes the CSF volume inside each compartment is redistributed. Cyclic compliance variation of brain tissue creates a pulsatile CSF flow. The CSF dynamics model is also used for the analysis of altered CSF dynamics; Normal Pressure Hydrocephalus and Idiopathic Intracranial Hypertension are explained as a consequence of altered compliance of the brain tissue

How growing tumour impacts intracranial pressure and deformation mechanics of brain

Brain is an actuator for control and coordination. When a pathology arises in cranium, it may leave a degenerative, disfiguring and destabilizing impact on brain physiology. However, the leading consequences of the same may vary from case to case. Tumour, in this context, is a special type of pathology which deforms brain parenchyma permanently. From translational perspective, deformation mechanics and pressures, specifically the intracranial cerebral pressure (ICP) in a tumour-housed brain, have not been addressed holistically in literature. This is an important area to investigate in neuropathy prognosis. To address this, we aim to solve the pressure mystery in a tumour-based brain in this study and present a fairly workable methodology. Using image-based finite-element modelling, we reconstruct a tumour-based brain and probe resulting deformations and pressures (ICP). Tumour is grown by dilating the voxel region by 16 and 30 mm uniformly. Cumulatively three cases are studied including an existing stage of the tumour. Pressures of cerebrospinal fluid due to its flow inside the ventricle region are also provided to make the model anatomically realistic. Comparison of obtained results unequivocally shows that as the tumour region increases its area and size, deformation pattern changes extensively and spreads throughout the brain volume with a greater concentration in tumour vicinity. Second, we conclude that ICP pressures inside the cranium do increase substantially; however, they still remain under the normal values (15 mmHg). In the end, a correlation relationship of ICP mechanics and tumour is addressed. From a diagnostic purpose, this result also explains why generally a tumour in its initial stage does not show symptoms because the required ICP threshold has not been crossed. We finally conclude that even at low ICP values, substantial deformation progression inside the cranium is possible. This may result in plastic deformation, midline shift etc. in the brain

Cerebrospinal Fluid Pulsations and Aging Effects in Mathematical Models of Hydrocephalus

In this Thesis we develop mathematical models to analyze two proposed causative mechanisms for the ventricular expansion observed in hydrocephalus: cerebrospinal fluid pulsations and small transmantle pressure gradients. To begin, we describe a single compartment model and show that such simple one-dimensional models cannot represent the complex dynamics of the brain. Hence, all subsequent models of this Thesis are spatio-temporal. Next, we develop a poroelastic model to analyze the fluid-solid interactions caused by the pulsations. Periodic boundary conditions are applied and the system is solved analytically for the tissue displacement, pore pressure, and fluid filtration. The model demonstrates that fluid oscillates across the brain boundaries. We develop a pore flow model to determine the shear induced on a cell by this fluid flow, and a comparison with data indicates that these shear forces are negligible. Thus, only the material stresses remain as a possible mechanism for tissue damage and ventricular expansion. In order to analyze the material stresses caused by the pulsations, we develop a fractional order viscoelastic model based on the linear Zener model. Boundary conditions appropriate for infants and adults are applied and the tissue displacement and stresses are solved analytically. A comparison of the tissue stresses to tension data indicates that these stresses are insufficient to cause tissue damage and thus ventricular expansion. Using age-dependent data, we then determine the fractional Zener model parameter values for infant and adult cerebra. The predictions for displacement and stresses are recomputed and the infant displacement is found to be unphysical. We propose a new infant boundary condition which reduces the tissue displacement to a physically reasonable value. The model stresses, however, are unchanged and thus the pulsation-induced stresses remain insufficient to cause tissue damage and ventricular expansion. Lastly, we develop a fractional hyper-viscoelastic model, based on the Kelvin- Voigt model, to obtain large deformation predictions. Using boundary conditions and parameter values for infants, we determine the finite deformation caused by a small pressure gradient by summing the small strain deformation resulting from pressure gradient increments. This iterative technique predicts that pediatric hydrocephalus may be caused by the long-term existence of small transmantle pressure gradients. We conclude the Thesis with a discussion of the results and their implications for hydrocephalus research as well as a discussion of future endeavors

Ventricle Equilibrium Position in Healthy and Normal Pressure Hydrocephalus Brains Using an Analytical Model

The driving force that causes enlargement of the ventricles remains unclear in case of normal pressure hydrocephalus (NPH). Both healthy and NPH brain conditions are characterized by a low transparenchymal pressure drop, typically 1 mm Hg. The present paper proposes an analytical model for normal and NPH brains using Darcy's and Biot's equations and simplifying the brain geometry to a hollow sphere with an internal and external radius. Self-consistent solutions for the large deformation problem that is associated with large ventricle dilation are presented and the notion of equilibrium or stable ventricle position is highlighted for both healthy and NPH conditions. The influence of different biomechanical parameters on the stable ventricle geometry is assessed and it is shown that both CSF seepage through the ependyma and parenchymal permeability play a key role. Although very simple, the present model is able to predict the onset and development of NPH conditions as a deviation from healthy conditions. [DOI: 10.1115/1.4006466

Mechanics of CSF in Human Ventricular System:Production and Circulation

Cerebrospinal fluid (CSF) is a water-like substance that circulates in a network of interconnected cavities located in the brain. The fluid ensures the brain’s well-being by providing hydromechanical and biochemical support. Moreover, the fluid facilitates neurogenesis (i.e. the birth of neurones); a process essential for embryo development and self-repair in developed brains. Changes in the composition or flow of CSF are linked to the development and progression of various neurological conditions such as hydrocephalus, multiple sclerosis, and Alzheimer’s disease. These conditions have been recognised for over a century; yet there is no definite explanation for their onset nor there is a cure to restore brain health. Hence, medical interventions (e.g. surgery, medication) are used to control the abnormalities and prevent further damage, but they do not address the underlying cause. One reason for the lack of effective treatments is the limited understanding of the CSF system; its production, circulation, and absorption, in healthy and diseased states, and after treatments. In this research, we aim to better understand the CSF system by conducting mathematical and computational modelling. At first, a comprehensive review of the existing literature is provided to bring to attention the controversies and misconceptions related to the system. Further, we discuss the necessity of exploring the system step by step to correct the existing conjectures. We present a novel and comprehensive mathematical model of the organ responsible for CSF production (i.e. choroid plexus (CP)). This model integrates the CP’s biological characteristics into physics and mathematical statements, which are solved using numerical techniques. The simulation predicts parameters such as pressure, concentration, and displacement of the CP, as well as the CSF production rate under different conditions such as ageing. This approach represents the first holistic method for understanding the dynamics of CSF production within the choroid plexus. This research is extended to a preliminary investigation of CSF circulation in a 3D computational model of the brain cavities, constructed from magnetic resonance images (MRI). Simulation results characterise the CSF flow by providing information on pressure gradients, wall shear stresses, and fluid velocitie

Cortical atrophy in chronic subdural hematoma from ultra-structures to physical properties

Several theories have tried to elucidate the mechanisms behind the pathophysiology of chronic subdural hematoma (CSDH). However, this process is complex and remains mostly unknown. In this study we performed a retrospective randomised analysis comparing the cortical atrophy of 190 patients with unilateral CSDH, with 190 healthy controls. To evaluate the extent of cortical atrophy, CT scan images were utilised to develop an index that is the ratio of the maximum diameter sum of 3 cisterns divided by the maximum diameter of the skull at the temporal lobe level. Also, we reported, for the first time, the ultrastructural analyses of the CSDH using a combination of immunohistochemistry methods and transmission electron microscopy techniques. Internal validation was performed to confirm the assessment of the different degrees of cortical atrophy. Relative Cortical Atrophy Index (RCA index) refers to the sum of the maximum diameter of three cisterns (insular cistern, longitudinal cerebral fissure and cerebral sulci greatest) with the temporal bones' greatest internal distance. This index, strongly related to age in healthy controls, is positively correlated to the preoperative and post-operative maximum diameter of hematoma and the midline shift in CSDH patients. On the contrary, it negatively correlates to the Karnofsky Performance Status (KPS). The Area Under the Receiver Operating Characteristics (AUROC) showed that RCA index effectively differentiated cases from controls. Immunohistochemistry analysis showed that the newly formed CD-31 positive microvessels are higher in number than the CD34-positive microvessels in the CSDH inner membrane than in the outer membrane. Ultrastructural observations highlight the presence of a chronic inflammatory state mainly in the CSDH inner membrane. Integrating these results, we have obtained an etiopathogenetic model of CSDH. Cortical atrophy appears to be the triggering factor activating the cascade of transendothelial cellular filtration, inflammation, membrane formation and neovascularisation leading to the CSDH formation

On the Validation of a Multiple-Network Poroelastic Model Using Arterial Spin Labeling MRI Data

The Multiple-Network Poroelastic Theory (MPET) is a numerical model to characterize the transport of multiple fluid networks in the brain, which overcomes the problem of conducting separate analyses on individual fluid compartments and losing the interactions between tissue and fluids, in addition to the interaction between the different fluids themselves. In this paper, the blood perfusion results from MPET modeling are partially validated using cerebral blood flow (CBF) data obtained from arterial spin labeling (ASL) magnetic resonance imaging (MRI), which uses arterial blood water as an endogenous tracer to measure CBF. Two subjects—one healthy control and one patient with unilateral middle cerebral artery (MCA) stenosis are included in the validation test. The comparison shows several similarities between CBF data from ASL and blood perfusion results from MPET modeling, such as higher blood perfusion in the gray matter than in the white matter, higher perfusion in the periventricular region for both the healthy control and the patient, and asymmetric distribution of blood perfusion for the patient. Although the partial validation is mainly conducted in a qualitative way, it is one important step toward the full validation of the MPET model, which has the potential to be used as a testing bed for hypotheses and new theories in neuroscience research

A multiple-network poroelastic model for biological systems and application to subject-specific modelling of cerebral fluid transport

Biological tissue can be viewed as porous, permeable and deformable media infiltrated by fluids, such as blood and interstitial fluid. A finite element model has been developed based on the multiple-network poroelastic theory to investigate transport phenomenon in such biological systems. The governing equations and boundary conditions are adapted for the cerebral environment as an example. The numerical model is verified against analytical solutions of classical consolidation problems and validated using experimental data of infusion tests. It is then applied to three-dimensional subject-specific modelling of brain, including anatomically realistic geometry, personalised permeability map and arterial blood supply to the brain. Numerical results of smoking and non-smoking subjects show hypoperfusion in the brains of smoking subjects, which also demonstrate that the numerical model is capable of capturing spatio-temporal fluid transport in biological systems across different scales